Seneca Valley Virus 3C pro Cleaves Heterogeneous Nuclear Ribonucleoprotein K to Facilitate Viral Replication

Jiangwei Song; Rong Quan; Dan Wang; Jue Liu

doi:10.3389/fmicb.2022.945443

Seneca Valley Virus 3C ^pro Cleaves Heterogeneous Nuclear Ribonucleoprotein K to Facilitate Viral Replication

Front Microbiol. 2022 Jul 6:13:945443. doi: 10.3389/fmicb.2022.945443. eCollection 2022.

Authors

Jiangwei Song¹, Rong Quan¹, Dan Wang¹, Jue Liu^{2

3}

Affiliations

¹ Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China.
² College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
³ Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.

Abstract

Seneca Valley virus (SVV) has emerged as an important pathogen that is associated with idiopathic vesicular infection in pigs, causing a potential threat to the global swine industry. The heterogeneous nuclear ribonucleoprotein K (hnRNP K) that shuttles between the nucleus and cytoplasm plays an important role in viral infection. In this study, we observed that infection with SVV induced cleavage, degradation, and cytoplasmic redistribution of hnRNP K in cultured cells, which was dependent on the activity of viral 3C^pro protease. Also, the 3C^pro induced degradation of hnRNP K via the caspase pathway. Further studies demonstrated that SVV 3C^pro cleaved hnRNP K at residue Q364, and the expression of the cleavage fragment hnRNP K (aa.365-464) facilitates viral replication, which is similar to full-length hnRNP K, whereas hnRNP K (aa.1-364) inhibits viral replication. Additionally, hnRNP K interacts with the viral 5' untranslated region (UTR), and small interfering RNA (siRNA)-mediated knockdown of hnRNP K results in significant inhibition of SVV replication. Overall, our results demonstrated that the hnRNP K positively regulates SVV replication in a protease activity-dependent fashion in which the cleaved C-terminal contributes crucially to the upregulation of SVV replication. This finding of the role of hnRNP K in promoting SVV propagation provides a novel antiviral strategy to utilize hnRNP K as a potential target for therapy.

Keywords: heterogeneous nuclear ribonucleoprotein K; host protein regulation; seneca valley virus; viral 3C protease; viral replication.